DE2926847A1 - BIS- (2-AMMONIUM-2-HYDROXYMETHYL-1,3-PROPANDIOL) SALT OF THE (2R-CIS) - (3-METHYLOXIRANYL) PHOSPHONIC ACID, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCT CONTAINING IT - Google Patents
BIS- (2-AMMONIUM-2-HYDROXYMETHYL-1,3-PROPANDIOL) SALT OF THE (2R-CIS) - (3-METHYLOXIRANYL) PHOSPHONIC ACID, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCT CONTAINING ITInfo
- Publication number
- DE2926847A1 DE2926847A1 DE19792926847 DE2926847A DE2926847A1 DE 2926847 A1 DE2926847 A1 DE 2926847A1 DE 19792926847 DE19792926847 DE 19792926847 DE 2926847 A DE2926847 A DE 2926847A DE 2926847 A1 DE2926847 A1 DE 2926847A1
- Authority
- DE
- Germany
- Prior art keywords
- cis
- salt
- hydroxymethyl
- phosphonic acid
- methyloxiranyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- YMDXZJFXQJVXBF-STHAYSLISA-N fosfomycin Chemical compound C[C@@H]1O[C@@H]1P(O)(O)=O YMDXZJFXQJVXBF-STHAYSLISA-N 0.000 title claims description 16
- 238000000034 method Methods 0.000 title claims description 4
- 238000004519 manufacturing process Methods 0.000 title description 3
- 229940126601 medicinal product Drugs 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 3
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 2
- YMDXZJFXQJVXBF-UHFFFAOYSA-N (3-methyloxiran-2-yl)phosphonic acid Chemical compound CC1OC1P(O)(O)=O YMDXZJFXQJVXBF-UHFFFAOYSA-N 0.000 claims 1
- 239000011230 binding agent Substances 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 159000000007 calcium salts Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 229960000308 fosfomycin Drugs 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- ZQNPDAVSHFGLIQ-UHFFFAOYSA-N calcium;hydrate Chemical compound O.[Ca] ZQNPDAVSHFGLIQ-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65502—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a three-membered ring
- C07F9/65505—Phosphonic acids containing oxirane groups; esters thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/62—Quaternary ammonium compounds
- C07C211/63—Quaternary ammonium compounds having quaternised nitrogen atoms bound to acyclic carbon atoms
Description
J. REITSTÖTTER & W. KINZEBACHJ. REITSTÖTTER & W. KINZEBACH
W. BUNTE (1958-1976) K. P. HÖLLERW. BUNTE (1958-1976) K. P. HÖLLER
TBLEPONl (Ο8Θ) 37 60 83 TELEXl B21B20B ISAR DTBLEPONl (Ο8Θ) 37 60 83 TELEXl B21B20B ISAR D
München, 3. Juli 1979 M/20 179Munich, July 3, 1979 M / 20 179
ZAMBON S.p.A. Via Lillo del Duca, 10 Mailand / ItalienZAMBON S.p.A. Via Lillo del Duca, 10 Milan / Italy
bis-(2-Ammonium-2-hydroxymethyl-1,3-propandiol)-Salz der (2R-cis)-(3-Methyloxiranyl )-phosphonsäure, Verfahren zu seiner Herstellung und dieses enthaltende Arzneimittelbis (2-ammonium-2-hydroxymethyl-1,3-propanediol) salt of (2R-cis) - (3-methyloxiranyl) -phosphonic acid, Process for its manufacture and medicament containing it
Die vorliegende Erfindung betrifft ein neues Salz der (2R-cis)-(3-Methyloxyranyl)phosphonsäure, dessen Herstellung und dieses enthaltende Arzneimittel.The present invention relates to a new salt of (2R-cis) - (3-methyloxyranyl) phosphonic acid, its preparation and medicaments containing them.
Die vorliegende Erfindung betrifft insbesondere das bis-(2-Ammonium-2-hydroxymethyl-i,3-propandiol)-Salz der (2R-cis)-(3-Methyloxiranyl)phosphonsäure der Formel:The present invention relates in particular to the bis (2-ammonium-2-hydroxymethyl-1,3-propanediol) salt of (2R-cis) - (3-methyloxiranyl) phosphonic acid of the formula:
HO-CH2 HO-CH 2
HO-CH9-C-NHo 2 , 3HO-CH 9 -C-NHo 2,3
HO-CH2 HO-CH 2
und dessen Herstellung.and its manufacture.
Die (2R-cis)-(3-Methyloxiranyl)phosphonsäure wird nachfolgend mit dem Trivialnamen Fosfomycin (Merck Index, 9. Auflage, 4110) bezeichnet. Die Natrium- und Calciumsalze von Fosfomycin werden in großem Umfange in der Human- und Veterinärmedizin verwendet, um das Wachstum von gram-positiven und gram-negativen pathogenen Bakterien zu verhindern.The (2R-cis) - (3-methyloxiranyl) phosphonic acid is used below referred to by the common name fosfomycin (Merck Index, 9th edition, 4110). The sodium and calcium salts of fosfomycin are used extensively in human and veterinary medicine to prevent the growth of gram-positive and gram-negative pathogenic bacteria.
Es wurde gefunden, daß das erfindungsgemäße Fosfomycin-Salz, das bis-(2-Ammonium-3-hydroxymethyl-1,3-propandiol )-Salz der (2R-cis)-(3-Methyloxiranyl)phosphonsäure sowohl eine erheblich bessere Verträglichkeit als auch eine erheblich bessere biologische Verfügbarkeit aufweist als die Natrium- und Calcium salze des Fosfömycins.It has been found that the fosfomycin salt according to the invention, the bis (2-ammonium-3-hydroxymethyl-1,3-propanediol) salt of (2R-cis) - (3-methyloxiranyl) phosphonic acid both a considerably better tolerance and a considerably better one exhibits bioavailability than the sodium and calcium salts of fosfömycin.
Insbesondere wurde gefunden, daß die biologische Verfügbarkeit des erfindungsgemäßen Fosfomycin-Salzes mindestens 200 % In particular, it has been found that the biological availability of the fosfomycin salt according to the invention is at least 200 %
(doppelt so groß) beträgt im Vergleich mit den anderen Fosfomy cin-Salzen, sowohl definiert als die im Urin bestimmte Antibio tikum-Gesantmenne als auch als die unter der Blutspiegel-Zeit-Kurve gebildeten Fläche. Die Herstellung des erfindungsgemäßen Fosfomycin-Salzes kann nach allgemeinen in der Chemie verwendeten und bekannten Verfahren hergestellt werden. Beispielsweise kann es durch eine doppelte Austauschreaktion zwischen dem Calciumsalzmonohydrat der (2R-cis)-(3-Methyloxiranyl)phosphonsäure und dem Oxalat des 2-Amino-2-hydroxymethyl-1,3-propandiols hergestellt werden.(twice as large) is in comparison with the other fosfomycin salts, both defined as the antibio determined in the urine tikum-Gesantmenne as well as the area formed under the blood level-time curve. The preparation of the fosfomycin salt according to the invention can generally be carried out in Chemistry used and known processes are produced. For example, it can be produced by a double exchange reaction between the calcium salt monohydrate of (2R-cis) - (3-methyloxiranyl) phosphonic acid and the oxalate of 2-amino-2-hydroxymethyl-1,3-propanediol.
Die Herstellung des erfindungsgemäßen Salzes wird durch das folgende Beispiel, das die vorliegende Erfindung jedoch in keiner Weise beschränken soll, näher erläutert.The preparation of the salt according to the invention is by the the following example, which is not intended to restrict the present invention in any way, is explained in more detail.
Zu 105,9 g des Monohydrates des Calciumsalzes der (2R-cis)-(3-Methyloxiranyl )phosphonsäure, welches in 320 ml Wasser suspendiert ist, werden bei 600C und unter Rühren eine Lösung aus 145 g 2-Amino-2-hydroxymethyl-1,3-propandiol und 49 g Oxalsäure in 270 ml Wasser stufenweise hinzugefügt.To 105.9 g of the monohydrate of the calcium salt of (2R-cis) - (3-Methyloxiranyl) phosphonic acid which is suspended in 320 ml of water are added a solution of 145 g at 60 0 C and with stirring, 2-amino-2- Hydroxymethyl-1,3-propanediol and 49 g of oxalic acid in 270 ml of water were gradually added.
Man läßt die Suspension auf Zimmertemperatur abkühlen, während 7 Stunden lang weiter gerührt wird.The suspension is allowed to cool to room temperature while stirring is continued for 7 hours.
Nach dem Stehen über Nacht bei 4°C, wird die Suspension unter Rühren und unter Vakuum über Theprite 5 (Handelsbezeichnung des Filtermaterials der Seitz-Filter-Werke) abfiltriert und das Filtrat bis zur Trockne eingeengt.After standing overnight at 4 ° C, the suspension is poured over Theprite 5 (trade name the filter material of the Seitz-Filter-Werke) and the filtrate was concentrated to dryness.
Der Rückstand wird mit 500 ml absolutem Äthylalkohol behandelt und unter Rühren 1 Stunde lang am Rückfluß gehalten. £119886/0636 The residue is treated with 500 ml of absolute ethyl alcohol and refluxed with stirring for 1 hour. £ 119886/0636
Das weiße kristalline Produkt, das nach dem Abkühlen ausfällt,
wird im Vakuum abfiltriert und im Vakuum 10 Stunden lang bei ; 600C getrocknet. ;The white crystalline product that precipitates after cooling
is filtered off in vacuo and in vacuo for 10 hours at; 60 0 C dried. ;
Es wurden 185 g des bis-(2-Ammonium-2-hydroxymethyl-1,3-pro- j
pandioD-Salzes der (2R-cis)-(3-Methyloxiranyl )phosphonsäure
erhalten.185 g of the bis (2-ammonium-2-hydroxymethyl-1,3-projectandioD salt of (2R-cis) - (3-methyloxiranyl) phosphonic acid were obtained
obtain.
Schmelzpunkt: 146 bis 148°C.Melting point: 146 to 148 ° C.
Die Elementaranalyse führte zu folgendem Ergebnis:
für C11H29N2O10PThe elemental analysis led to the following result:
for C 11 H 29 N 2 O 10 P
= "3l3° (c = 10 = " 3l3 ° (c = 10
lü/v· 909886/0636lü / v 909886/0636
Claims (3)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT25853/78A IT1112282B (en) | 1978-07-19 | 1978-07-19 | Bis- (2-AMMONIUM-2-hydroxymethyl-1,3-propanediol) (2R-CIS) - (3-METILOSSIRANIL) phosphonate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE2926847A1 true DE2926847A1 (en) | 1980-02-07 |
| DE2926847C2 DE2926847C2 (en) | 1988-11-10 |
Family
ID=11217928
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19792926847 Granted DE2926847A1 (en) | 1978-07-19 | 1979-07-03 | BIS- (2-AMMONIUM-2-HYDROXYMETHYL-1,3-PROPANDIOL) SALT OF THE (2R-CIS) - (3-METHYLOXIRANYL) PHOSPHONIC ACID, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCT CONTAINING IT |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US4727065A (en) |
| JP (1) | JPS5517381A (en) |
| AT (1) | AT371823B (en) |
| AU (1) | AU526464B2 (en) |
| BE (1) | BE877286A (en) |
| CA (1) | CA1108631A (en) |
| CH (1) | CH640823A5 (en) |
| DE (1) | DE2926847A1 (en) |
| DK (1) | DK148023C (en) |
| ES (1) | ES482268A1 (en) |
| FR (1) | FR2431506A1 (en) |
| GB (1) | GB2025975B (en) |
| GR (1) | GR75071B (en) |
| IE (1) | IE48781B1 (en) |
| IL (1) | IL57680A (en) |
| IT (1) | IT1112282B (en) |
| LU (1) | LU81500A1 (en) |
| NL (1) | NL190488C (en) |
| SE (1) | SE440360B (en) |
| YU (1) | YU41411B (en) |
| ZA (1) | ZA793354B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3203937A1 (en) * | 1982-02-05 | 1983-09-01 | Luc Dr Barrut | METHOD AND DEVICE FOR MECHANICAL RESTORATION OR CORRECTION OF AT LEAST ONE TOOTH OR FOR MACHINE PREPARATION OF AT LEAST ONE TOOTH FOR A FIXED PROSTHETIC RESTORATION AND MACHINE-MAKING THE FIXED PRESIDENT RETURNS |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1124610B (en) * | 1979-10-18 | 1986-05-07 | Zambo Spa | MONO (2-AMMONIUM-2-HYDROXYMETHYL-1,3-PROPANDIOL) (2R-CIS) - (O-METHYLOXYRANYL) PHOSPHONATE |
| IT1136652B (en) * | 1981-06-04 | 1986-09-03 | Crinos Industria Farmaco | PHARMACEUTICAL COMPESITION OF PHOSPHOMYCIN IN TABLETS TO SUCK |
| CH660306A5 (en) * | 1984-10-05 | 1987-04-15 | Schering Spa | WATER-SOLUBLE PHARMACEUTICAL COMPOSITIONS BASED ON SALTS OF (-)CIS-1,2-EPOXYPROPYLPHOSPHONIC ACID WITH AMINO ACIDS. |
| CH660305A5 (en) * | 1984-10-05 | 1987-04-15 | Schering Spa | WATER-SOLUBLE PHARMACEUTICAL COMPOSITIONS BASED ON SALTS OF (-)CIS-1,2-EPOXYPROPYLPHOSPHONIC ACID WITH AMINO ACIDS. |
| IT1231013B (en) * | 1989-07-27 | 1991-11-08 | Zambon Spa | MONO (2 AMMONIUM 2 HYDROXYMETHYL 1,3 PROPANDIOL) (2R, CIS) 1,2 EPOSSIPROPIL PHOSPHONATE HAVING IMPROVED STABILITY AND WORKABILITY CHARACTERISTICS. |
| US5191094A (en) * | 1989-07-27 | 1993-03-02 | Zambon Group S.P.A. | Mono (2-ammonium-2-hydroxymethyl-1,3-propanediol) (2R,cis)-1,2-epoxypropyl-phosphonate with improved characteristics of stability and processing |
| ITMI20021725A1 (en) * | 2002-08-01 | 2002-10-31 | Zambon Spa | PHARMACEUTICAL COMPOSITIONS WITH ANTIBIOTIC ACTIVITY. |
| EP1762573A1 (en) | 2005-09-08 | 2007-03-14 | Interquim, S.A. De C.V. | A process for the preparation of fosfomycin salts |
| ES2385158B1 (en) * | 2010-12-24 | 2013-05-28 | Arafarma Group, S.A. | PHARMACEUTICAL PHOSPHOMYCIN COMPOSITION |
| CN102807586B (en) | 2012-08-31 | 2015-05-13 | 东北制药集团股份有限公司 | Preparation method of fosfomycin amine salt |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1768965B1 (en) * | 1967-07-25 | 1971-12-23 | Merck & Co Inc | (-) - (cis-1,2-Epoxypropyl) -phosphonic acid and its salts and processes for the preparation of these compounds |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3641063A (en) * | 1968-01-22 | 1972-02-08 | Merck & Co Inc | Antibiotic purification process |
-
1978
- 1978-07-19 IT IT25853/78A patent/IT1112282B/en active
-
1979
- 1979-06-25 GB GB7922098A patent/GB2025975B/en not_active Expired
- 1979-06-26 BE BE0/195974A patent/BE877286A/en not_active IP Right Cessation
- 1979-06-27 CH CH601579A patent/CH640823A5/en not_active IP Right Cessation
- 1979-06-27 IL IL57680A patent/IL57680A/en unknown
- 1979-06-29 AU AU48552/79A patent/AU526464B2/en not_active Expired
- 1979-07-02 GR GR59481A patent/GR75071B/el unknown
- 1979-07-03 DE DE19792926847 patent/DE2926847A1/en active Granted
- 1979-07-05 YU YU1632/79A patent/YU41411B/en unknown
- 1979-07-05 FR FR7917455A patent/FR2431506A1/en active Granted
- 1979-07-05 ZA ZA793354A patent/ZA793354B/en unknown
- 1979-07-06 ES ES482268A patent/ES482268A1/en not_active Expired
- 1979-07-11 AT AT0484079A patent/AT371823B/en not_active IP Right Cessation
- 1979-07-13 LU LU81500A patent/LU81500A1/en unknown
- 1979-07-18 JP JP9046879A patent/JPS5517381A/en active Granted
- 1979-07-18 SE SE7906172A patent/SE440360B/en unknown
- 1979-07-18 DK DK302379A patent/DK148023C/en not_active IP Right Cessation
- 1979-07-19 CA CA332,193A patent/CA1108631A/en not_active Expired
- 1979-07-19 NL NLAANVRAGE7905635,A patent/NL190488C/en not_active IP Right Cessation
- 1979-08-08 IE IE1366/79A patent/IE48781B1/en not_active IP Right Cessation
-
1986
- 1986-01-23 US US06/824,922 patent/US4727065A/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1768965B1 (en) * | 1967-07-25 | 1971-12-23 | Merck & Co Inc | (-) - (cis-1,2-Epoxypropyl) -phosphonic acid and its salts and processes for the preparation of these compounds |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3203937A1 (en) * | 1982-02-05 | 1983-09-01 | Luc Dr Barrut | METHOD AND DEVICE FOR MECHANICAL RESTORATION OR CORRECTION OF AT LEAST ONE TOOTH OR FOR MACHINE PREPARATION OF AT LEAST ONE TOOTH FOR A FIXED PROSTHETIC RESTORATION AND MACHINE-MAKING THE FIXED PRESIDENT RETURNS |
Also Published As
| Publication number | Publication date |
|---|---|
| IE791366L (en) | 1980-01-19 |
| NL190488C (en) | 1994-03-16 |
| DK148023C (en) | 1985-07-08 |
| FR2431506B1 (en) | 1984-11-23 |
| FR2431506A1 (en) | 1980-02-15 |
| JPS5517381A (en) | 1980-02-06 |
| DK302379A (en) | 1980-01-20 |
| IT7825853A0 (en) | 1978-07-19 |
| IE48781B1 (en) | 1985-05-15 |
| ZA793354B (en) | 1980-07-30 |
| GR75071B (en) | 1984-07-13 |
| BE877286A (en) | 1979-12-27 |
| CA1108631A (en) | 1981-09-08 |
| NL190488B (en) | 1993-10-18 |
| IT1112282B (en) | 1986-01-13 |
| IL57680A (en) | 1986-01-31 |
| SE7906172L (en) | 1980-01-20 |
| CH640823A5 (en) | 1984-01-31 |
| IL57680A0 (en) | 1979-10-31 |
| YU41411B (en) | 1987-04-30 |
| ATA484079A (en) | 1982-12-15 |
| AU526464B2 (en) | 1983-01-13 |
| SE440360B (en) | 1985-07-29 |
| DK148023B (en) | 1985-02-04 |
| LU81500A1 (en) | 1979-10-31 |
| US4727065A (en) | 1988-02-23 |
| DE2926847C2 (en) | 1988-11-10 |
| AU4855279A (en) | 1980-01-24 |
| GB2025975B (en) | 1983-02-02 |
| YU163279A (en) | 1983-02-28 |
| GB2025975A (en) | 1980-01-30 |
| ES482268A1 (en) | 1980-04-16 |
| NL7905635A (en) | 1980-01-22 |
| JPS6248678B2 (en) | 1987-10-15 |
| AT371823B (en) | 1983-08-10 |
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